Chlamydia trachomatis is an obligate intracellular bacterium responsible for causing the most cases of bacterial sexually transmitted disease. Three million new cases occur in the US each year and the majority are asymptomatic and not treated. Untreated, persistent infection or reinfection results in pelvic inflammatory disease (PID), ectopic pregnancy & tubal infertility and cost the health care industry billions of dollars annually. The immune response against C. trachomatis is in part responsible for the reproductive dysfunction. The chemokine, CXCL13, is secreted within tissues during an immune response and is important for assembling and organizing lymph aggregates within tissues. CXCL13 is only temporarily secreted by non-diseased tissues and continual secretion has been postulated to maintain the presence of ectopic lymphoid structures and indicates the presence of an ongoing immune response. Intriguingly, the presence of ectopic lymphoid aggregates within fallopian tubes is diagnostic for salpingitis, a condition which precedes tubal infertility. We found that infection of upper genital tract (UGT) tissue with C. trachomatis induces expression of CXCL13 which is not routinely present in fallopian tubes and its secretion is modulated by progesterone. CXCL13 secretion reduces the magnitude of post-infection inflammation within the murine UGT while not interfering with bacterial elimination. We hypothesize that CXCL13 attracts a CXCR5+ cell to the UGT and this cell is indispensable for preventing inflammation in the female UGT. Interference with this interaction causes continual recruitment of inflammatory T cells and could contribute to infertility. We propose the following specific aims to test this hypothesis, 1) Investigate the extent of the CXCL13-CXCR5 axis in regulating inflammation in vivo. 2) Identify the mechanism(s) whereby C. trachomatis induces CXCL13 within human UGT cells. 3) Evaluate the extent of progesterone in modulating CXCL13 expression after infection. We will employ in vivo mouse experiments to identify the phenotype & function of CXCR5+ cells. Also, we will investigate host-pathogen interaction with human UGT epithelial cells using real-time PCR, ELISA assays and NFkB pathway analysis. CXCL13 may be a regulator of inflammation following a Chlamydia genital infection. Insight into CXCL13 secretion will impact public health and the welfare of women in the US by aiding the development of therapeutics to prevent tubal infertility.